A $20.7M federal grant will fund a 5-year inhaled vaccines initiative at the Icahn School of Medicine at Mount Sinai beginning with development of an avian influenza nasal spray prototype.
RT’s Three Key Takeaways:
- Federal Project Award: Researchers at the Icahn School of Medicine at Mount Sinai received a five-year agreement valued at approximately $20.7 million to develop a new vaccine platform targeting respiratory threats.
- Targeted Nasal Technology: The research begins with an unmodified mRNA nasal vaccine prototype against avian influenza that directs antigen delivery specifically to immune cells in the respiratory tract.
- Broad Pathogen Defense: Following initial validation, the program aims to expand into a multivalent strategy designed to protect against at least 20 respiratory viruses.
Researchers at the Icahn School of Medicine at Mount Sinai have been awarded a five-year project agreement valued at approximately $20.7 million to establish Vaccine Immunoengineering for Targeted Antigen Presentation and Layered Control (VITAL), an initiative exploring improved immunization methods against respiratory pathogens, according to a news release from the Mount Sinai Health System.
The project is backed by the Defense Threat Reduction Agency (DTRA) Joint Science and Technology Office (JSTO) through the Medical CBRN Defense Consortium, with incremental funding scheduled through August 28, 2031. VITAL was selected under JSTO’s Reimagining Available Vaccines and Envisioning Novelty (RAVEN) program, which supports multivalent biological countermeasures capable of addressing multiple threats rather than individual pathogens.
Targeting Respiratory Immune Cells
The initial proof of concept focuses on highly pathogenic avian influenza A virus (H5N1). Investigators are developing an unmodified mRNA-based vaccine prototype designed for intranasal delivery. The platform restricts immunogen expression primarily to macrophages in the respiratory tract, aiming to prevent adverse events associated with antigen expression in non-immune cells that do not participate in clearance during natural infection, according to the health system.
“VITAL is designed to directly support RAVEN’s objective by asking a broader question than whether we can make a vaccine against one virus,” said Gustavo Palacios, PhD, professor of microbiology at the Icahn School of Medicine and VITAL project lead, in a news release. “Rather than focusing only on which antigens are delivered, we want to understand which biological principles can be incorporated into vaccination so that the same framework can eventually be adapted across different respiratory threats. H5N1 gives us a rigorous starting point to test those principles.”
The VITAL framework relies on five core biological principles: restricting immunogen expression to immune cells, providing appropriate immune stimulation, engineering antigens to reduce toxicity, aligning delivery with the natural route of infection, and using pulse immunization schedules to mimic natural pathogen exposure patterns. Antigen detoxification serves as a central element, modifying viral antigens to limit adverse reactions while preserving immunogenicity and expression, Mount Sinai reported.
Expanding Long-Term Respiratory Protection
“One of the central challenges in influenza vaccination is achieving protection that is broad and durable rather than narrowly focused on a single circulating influenza virus variant,” said Adolfo Garcia-Sastre, PhD, professor of medicine and director of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine, in a news release. “VITAL gives us an opportunity to explore a different way of approaching that problem—by engineering not only the antigen, but also how, where, and over what time course the immune system encounters it.”
To evaluate immune responses, researchers will integrate animal models with human primary immune tissue models, including tonsil-based systems, alongside spatial analysis, single-cell profiling, proteomics, and computational tools. The team will assess how targeted antigen-presenting cells, such as macrophages and dendritic cells, interact to generate downstream B cell and T cell activity.
“A major strength of VITAL is the ability to study how vaccination shapes the immune response in physiologically relevant human systems,” said Ana Fernandez-Sesma, PhD, chair of the department of microbiology at the Icahn School of Medicine, in a news release. “By looking closely at macrophages, dendritic cells, and other immune populations using primary human tissues, we can predict whether a vaccine generates the appropriate immune response in humans as an alternative to animal models.”
If the initial H5N1 prototype proves successful, the team plans to expand the platform into a multivalent candidate covering at least 20 respiratory viruses, according to Mount Sinai. Preclinical testing across young and aged animal models and human tissue systems will support regulatory planning and Investigational New Drug (IND)-enabling activities for future clinical translation.
